Atherosclerotic sequelae, such as peripheral arterial occlusion disease, coronary artery disease as well as the apoplectic cerebral insultus, are still among the main causes of death in the United States, Europe, and in large parts of Asia. In particular, coronary artery disease (CAD) is the leading cause of mortality in the U.S., and the cause of death for one in 2.7 Americans.
The development of the atherosclerosis is considered to be a chronic progressive inflammation of the arterial vessel wall which is characterized by a complex interaction of growth factors, cytokines and cell interactions. In general, LDLs and other proteins become oxidized, bind and activate endothelial cells and then move into the tissue surrounding the vasculature. Macrophages bind to the activated endothelial cells and infiltrate into the area. Scavenger receptors (SRs) on macrophages and endothelial cells bind and internalize these materials forming “foam cells”. Lipid peroxidation occurs and more LDLs and proteins are oxidized that bind to the endothelial macrophages. The expression of endothelial adhesion molecules such as selectins, integrins, ICMA-1, VCAM-1 and platelet-endothelial-cell adhesion molecule-1, and the like, mediate adhesion of monocytes and T-lymphocytes in the lumen and inflammatory cytokines/chemokines (e.g., IL-6, CRP, TNF, IL-1, etc.) are released. Eventually substantial cellular apoptosis/necrosis occurs. The plaque becomes unstable and ultimately the cap is destroyed.
Importantly, 70% of individuals who are 40 years of age and older have CAD, however, it is subclinical with no physical symptoms. As well, there is no currently available non-invasive testing that is able to identify these CAD individuals. Invasive testing (e.g., cardiac catheterization) of these patients to determine the presence of non-obstructive and subclinical CAD is contraindicated. Non-invasive imaging including computed tomography (CT) and magnetic resonance (MR) coronary angiography (CTA and MRA) are not reliable in the detecting these CAD lesions.